crossing96/oncoscreening huggingface dataset:
Head and neck squamous cell carcinoma and metachronous second primaries.	OBJECTIVES: To assess the rate of second (or more) primaries after treatment for head and neck squamous cell carcinoma (HNSCC), and survival compared to patients with a single head and neck cancer. MATERIAL AND METHOD: A single-center retrospective study was performed in a University Hospital Center in 541 patients between 2002 and 2010. RESULTS: One hundred and forty-one patients (26.06%) presented 172 metachronous cancers. Overall 5-year survival was 20.3% with and 38.1% without metachronous cancer. Median and mean survival were respectively 21.9 and 51 months in patients with a single cancer, versus 13.9 and 26.5 months in case of metachronous cancer. Specific survival was comparable to overall survival. All-cause and specific survival were significantly poorer in metachronous cancer (P=0.001; log-rank α=0.05). CONCLUSION: At least a quarter of HNSCC patients go on to develop a metachronous second primary. These are of poor prognosis, whatever their location.	bladder
Resection of the urinary bladder for locally advanced colorectal cancer: a retrospective comparison of partial versus total cystectomy.	BACKGROUND: The postoperative and survival outcomes of patients with primary advanced colorectal cancer who undergo partial versus total cystectomy have not been adequately compared, as studies of this topic are rare and comprise relatively small cohorts. This study aimed to investigate the short- and long-term outcomes of patients who underwent en bloc partial or total cystectomy for primary advanced colorectal cancer that was suspected of adhering to or invading the urinary bladder. METHODS: The study included 90 patients who underwent various degrees of cystectomy between 1993 and 2013 to treat locally advanced primary colorectal cancer that was suspected of involving the urinary bladder. Patients in whom total cystectomy was performed solely because of prostate-invading lower rectal cancer were excluded. Data on patient characteristics and their short- and long-term outcomes were collected retrospectively to evaluate differences between partial cystectomy (the P group; n = 72) and total cystectomy (the T group; n = 18). Postoperative and oncologic outcomes were also analyzed. RESULTS: The T group had significantly greater operating times than the P group (median, 572 vs. 346 min); blood loss volume was also greater in the T group (median, 3092 vs. 1112 mL). The postoperative overall complication rate was significantly greater in the T group than in the P group (94.4% vs. 51.4%). With a median follow-up duration of 62 months, local recurrences were observed in 22.2 and 6.9% of patients in the T and P groups, respectively. On multivariate Cox regression analyses using partial cystectomy as the reference, total cystectomy was independently associated with poorer local recurrence-free survival (hazard ratio [HR], 4.0 95% confidence interval [CI], 1.1-15.0), relapse-free survival (HR, 2.9; 95% CI, 1.2-6.9), and overall survival (HR, 2.1; 95% CI, 1.0-4.3). CONCLUSIONS: Patients who undergo en bloc total cystectomy for locally advanced colorectal cancers have worse postoperative and oncologic outcomes than those who undergo partial cystectomy.	bladder
Post-translational inhibition of YAP oncogene expression by 4-hydroxynonenal in bladder cancer cells.	The transcriptional regulator YAP plays an important role in cancer progression and is negatively controlled by the Hippo pathway. YAP is frequently overexpressed in human cancers, including bladder cancer. Interestingly, YAP expression and activity can be inhibited by pro-oxidant conditions; moreover, YAP itself can also affect the cellular redox status through multiple mechanisms. 4-Hydroxynonenal (HNE), the most intensively studied end product of lipid peroxidation, is a pro-oxidant agent able to deplete GSH and has an anti-tumoral effect by affecting multiple signal pathways, including the down-regulation of oncogene expressions. These observations prompted us to investigate the effect of HNE on YAP expression and activity. We demonstrated that HNE inhibited YAP expression and its target genes in bladder cancer cells through a redox-dependent mechanism. Moreover, the YAP down-regulation was accompanied by an inhibition of proliferation, migration, invasion, and angiogenesis, as well as by an accumulation of cells in the G2/M phase of cell cycle and by an induction of apoptosis. We also established the YAP role in inhibiting cell viability and inducing apoptosis in HNE-treated cells by using an expression vector for YAP. Furthermore, we identified a post-translational mechanism for the HNE-induced YAP expression inhibition, involving an increase of YAP phosphorylation and ubiquitination, leading to proteasomal degradation. Our data established that HNE can post-translationally down-regulate YAP through a redox-dependent mechanism and that this modulation can contribute to determining the specific anti-cancer effects of HNE.	bladder
Alcohol Drinking and Bladder Cancer Risk From a Pooled Analysis of Ten Cohort Studies in Japan.	BACKGROUND: The association of alcohol drinking with bladder cancer risk remains unclear in East Asian populations. Aldehyde dehydrogenase 2 (ALDH2) enzyme oxidizes alcohol-metabolized carcinogenic acetaldehyde into acetate. It is well known that the inactive ALDH2 carriers, specific to East Asian populations, have an increased risk of several cancer types because of increased exposure to acetaldehyde after alcohol consumption. The aim of this study was to examine the association between alcohol drinking and bladder cancer risk using data from ten population-based prospective cohort studies in Japan, where approximately 40% of the population has inactive ALDH2 enzyme. METHODS: We analyzed 340,497 Japanese participants with average follow-up of 13.4 years. The association between alcohol drinking and bladder cancer risk was evaluated using Cox regression models within each study, and random-effects models were used to estimate pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). RESULTS: During 4,729,071 person-years, 936 men and 325 women were newly diagnosed with bladder cancer. Our results showed no evidence of significant association between alcohol drinking and bladder cancer risk even among men who consumed alcohol of ≥69 g/week, with HR of 1.02 (95% CI, 0.79-1.33). The null result was observed consistently among women. CONCLUSIONS: Our findings do not support an association between alcohol drinking and bladder cancer risk in the Japanese, at least without consideration of the polymorphisms of alcohol-metabolizing enzymes.	bladder
Tumor Location May Predict Adverse Pathology and Survival Following Definitive Treatment for Bladder Cancer: A National Cohort Study.	BACKGROUND: While urothelial carcinoma of the bladder is often considered a multifocal disease, the location of the dominant tumor may be prognostic. OBJECTIVE: To determine the association between intravesical tumor location and both adverse pathological outcomes as well as overall survival. DESIGN, SETTINGS, AND PARTICIPANTS: Patients in the National Cancer Database (2010-2015) with nonmetastatic urothelial carcinoma of the bladder who underwent primary treatment with radical cystectomy (RC; n=3464) or chemoradiotherapy (CRT; n=699). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regressions assessed the prognostic ability of tumor location to predict adverse pathology at RC (nodal metastases [pN+] or advanced stage [pT3-4]). Cox regressions were used to determine the effect of tumor location on overall survival in patients treated with RC or CRT. RESULTS AND LIMITATIONS: Following RC, 822 (24%) patients were pN+ and 1551 (55%) were pT3-4. Trigonal tumors were most likely to have adverse pathology (31% pN+ and 59% pT3-4), while anterior wall tumors were the least (19% pN+ and 50% pT3-4). Relative to the anterior wall, trigone (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.12-2.43, p=0.012) and bladder neck (OR 1.79, 95% CI 1.11-2.90, p=0.018) tumors were associated with increased odds of pN+ and dome (OR 1.56, 95% CI 1.08-2.24, p=0.017) with pT3-4. In those patients treated with primary CRT, trigone involvement was associated with worse survival (HR 1.58, 95% CI 1.17-2.13, p=0.003). Limitations included unmeasured variables and a relatively few number of patients with certain tumor locations. CONCLUSIONS: Trigone and bladder neck tumors are associated with increased odds of nodal involvement, and dome with a higher tumor stage at RC. Patients with trigone involvement may have worse overall survival following CRT. PATIENT SUMMARY: Location of the tumor within the bladder may be associated with worse cancer staging at the time of the surgery and worse survival following chemoradiotherapy.	bladder
Mouse Models of Muscle-invasive Bladder Cancer: Key Considerations for Clinical Translation Based on Molecular Subtypes.	CONTEXT: In the past few years, research has suggested that molecular subtypes in muscle-invasive bladder cancer (MIBC) may be exploited to accelerate developments in clinical disease management and novel therapeutics. OBJECTIVE: To review MIBC mouse models from a molecular subtype perspective, their advantages and limitations, and their applications in translational medicine, based on a PubMed search for publications from January 2000 to February 2018. EVIDENCE ACQUISITION: Publications relevant to MIBC mouse models and their molecular subtypes were identified in a literature review. EVIDENCE SYNTHESIS: We classified the models according to the technique used for their establishment. For xenotransplant and allograft models, the inoculated cells and inoculated locations are the major determinants of molecular subtypes. Although the cell lines used in xenotransplant models can cover most of the basal-squamous and luminal subtypes, allograft models offer a more realistic environment in which to reconstruct aspects of the associated stromal and immune features. Autochthonous models, using genetic and/or chemical stimuli to induce disease progression, can also generate models with basal-squamous and luminal subtypes, but further molecular characterisation is needed since other mutational variants may be introduced in these models. CONCLUSIONS: We identified preclinical MIBC models with different subtype specifications and assessed their promise and current limitations. These models are versatile tools that can reproduce the molecular complexity of MIBC and support novel therapeutic development. PATIENT SUMMARY: Understanding which models of muscle-invasive bladder cancer most accurately represent the clinical situation is important for the development of novel drugs and disease management strategies. We review the different models currently available and their relevance to different clinical subtypes.	bladder
Survival Benefit Persists With Delayed Initiation of Adjuvant Chemotherapy Following Radical Cystectomy for Locally Advanced Bladder Cancer.	OBJECTIVE: To determine if delaying the initiation of adjuvant chemotherapy following radical cystectomy for locally advanced bladder cancer worsens overall survival. METHODS: This is a retrospective cohort study utilizing the National Cancer Database from 2006 to 2013. We included treatment-naïve patients who underwent radical cystectomy for muscle-invasive bladder cancer found to have locally advanced disease (pT3-T4 and/or pN+). Patients received no chemotherapy or multiagent adjuvant chemotherapy between 30 and 180 days following surgery. We used a multivariable Cox Regression to assess for differences in overall survival according to when patients initiated adjuvant chemotherapy. RESULTS: We identified 3590 patients: 2581 received no chemotherapy and 1009 received multiagent adjuvant chemotherapy. Adjuvant chemotherapy began 31-60 days postsurgery in 538 patients, 61-90 days in 321 patients, and 91-180 days in 150 patients. Relative to patients who did not receive chemotherapy, adjuvant chemotherapy decreased mortality when started 31-60 days (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.52-0.69; P <.001), 61-90 days (HR, 0.62; 95% CI, 0.53-0.74; P <.001), and 91-180 days following radical cystectomy (HR, 0.69; 95% CI, 0.55-0.87; P = .002). CONCLUSION: Adjuvant chemotherapy offers a survival benefit when started up to 6 months after radical cystectomy in patients with high-risk disease who did not receive neoadjuvant chemotherapy. Patients who require delayed initiation of adjuvant chemotherapy can still benefit from treatment.	bladder
Dynamic Regulation of Caveolin-1 Phosphorylation and Caveolae Formation by Mammalian Target of Rapamycin Complex 2 in Bladder Cancer Cells.	The mammalian target of rapamycin (mTOR) and associated phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway is commonly up-regulated in cancer, including bladder cancer. mTOR complex 2 (mTORC2) is a major regulator of bladder cancer cell migration and invasion, but the mechanisms by which mTORC2 regulates these processes are unclear. A discovery mass spectrometry and reverse-phase protein array-based proteomics dual approach was used to identify novel mTORC2 phosphoprotein targets in actively invading cancer cells. mTORC2 targets included focal adhesion kinase, proto-oncogene tyrosine-protein kinase Src, and caveolin-1 (Cav-1), among others. Functional testing shows that mTORC2 regulates Cav-1 localization and dynamic phosphorylation of Cav-1 on Y14. Regulation of Cav-1 activity by mTORC2 also alters the abundance of caveolae, which are specialized lipid raft invaginations of the plasma membrane associated with cell signaling and membrane compartmentalization. Our results demonstrate a unique role for mTORC2-mediated regulation of caveolae formation in actively migrating cancer cells.	bladder
Organ preservation in bladder cancer: an opportunity for truly personalized treatment.	Radical treatment of many solid tumours has moved from surgery to multimodal organ preservation strategies combining systemic and local treatments. Trimodality bladder-preserving treatment (TMT) comprises maximal transurethral resection of the bladder tumour followed by radiotherapy and concurrent radiosensitizing treatment, thereby sparing the urinary bladder. From the patient's perspective, the choice of maintaining quality of life without a negative effect on the chances of cure and long-term survival is attractive. In muscle-invasive bladder cancer (MIBC), the evidence shows comparable clinical outcomes between patients undergoing radical cystectomy and TMT. Despite this evidence, many patients continue to be offered radical surgery as the standard-of-care treatment. Improvements in radiotherapy techniques with adaptive radiotherapy and advances in imaging translate to increases in the accuracy of treatment delivery and reductions in long-term toxicities. With the advent of novel biomarkers promising improved prediction of treatment response, stratification of patients for different treatments on the basis of tumour biology could soon be a reality. The future of oncological treatment lies in personalized medicine with the combination of technological and biological advances leading to truly bespoke management for patients with MIBC.	bladder
let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1.	BACKGROUND: Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells. METHODS: Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i. RESULTS: Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637. CONCLUSIONS: Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.	bladder
[Personalised medicine in urothelial bladder cancer].	Available treatment options and outcomes for patients suffering from urothelial bladder cancer, especially in the metastatic stage, have hardly improved over decades. However, the increasing use of high-throughput analyses and the concept of immune surveillance against tumours have recently changed our understanding of tumour biology in terms of tumour development and progression. Our knowledge of genetic mutations and molecular subtypes provides the possibility of tailor-made therapeutic approaches for patients suffering from bladder cancer. For example, changes in DNA repair signalling pathways are possible predictors of chemotherapy response, and targeted therapies using FGFR or PARP inhibitors are currently being tested in clinical trials. The extent to which molecular subtypes will find their way into clinical practice depends on the prospective evaluation of their prognostic and predictive value. The introduction of immune checkpoint inhibitors is probably the most significant expansion of available treatment options in bladder cancer. Despite their promising results, however, a lot of questions remain to be answered, as only 25 % of patients respond. Again, this highlights the need for predictive biomarkers. The large inter- and intratumoural heterogeneity represents a particular challenge for the clinical implementation of personalised treatment options in bladder cancer. All in all, some important steps towards personalised medicine in urothelial bladder cancer have been taken in the past few years, but, for the most part, their prospective evaluation is still pending.	bladder
[Low frequency of cancer in the urinary organs when macroscopic hematuria is associated with bacteriuria].	Frequency of cancer in the urinary organs was significantly lower in patients with macroscopic hematuria associated with bacteriuria compared to those without bacteriuria. The predictive value of macroscopic hematuria was <1% in patients ≤ 75 years of age with concomitant bacteriuria. CT-urography added no diagnostic value over and above cystoscopy in patients with macroscopic hematuria with bacteriuria.Bacteriuria with other bacteria than E. coli or S. saprophyticus was associated with findings of bladder tumors.	bladder
Alterations of Antioxidant Enzymes and Biomarkers of Nitro-oxidative Stress in Tissues of Bladder Cancer.	Bladder cancer (BC) is one of the most common tumors found in the urinary bladder for both male and female in western countries. In vitro and in vivo studies suggest that high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and oxidative stress play a crucial role in human cancer. Low concentration of ROS and RNS is indispensable for cell survival and proliferation. However, high concentration of ROS and RNS can exert a cytotoxic effect. Increased oxidative stress is a result of either increased ROS/RNS production or a decrease of antioxidant defense mechanisms. A literature search was carried out on PubMed, Medline, and Google Scholar for articles in English published up to May 2018 using the following keywords: oxidative stress, antioxidants, reactive oxygen species, lipid peroxidation, paraoxonase, urinary bladder cancer, and nitric oxide. Literature data demonstrate that BC is associated with oxidative stress and with an imbalance between oxidants and antioxidant enzymes. Markers of lipid peroxidation, protein and nucleic acid oxidation are significantly higher in tissues of patients with BC compared with control groups. A decrease of activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione, and paraoxonase) has also been demonstrated. The imbalance between oxidants and antioxidants could have a potential role in the etiology and progression of bladder cancer.	bladder
Intrinsic Molecular Subclassification of Urothelial Carcinoma of the Bladder: Are We Finally there?	Bladder cancer is a highly prevalent disease throughout the world usually encountered in older patients, and associated with substantial morbidity, mortality, and cost. The treatment of bladder cancer has remained unchanged for the last several decades. However, in recent years the availability of comprehensive genomic data from The Cancer Genome Atlas and other large projects have considerably improved our understanding of the pathogenesis of these tumors. These studies demonstrated that bladder cancers can be grouped into 2 broad categories namely basal and luminal molecular subtypes with recognizable subgroups in each of these categories. Clinical data suggest that invasive basal cancers are more sensitive to neoadjuvant chemotherapy (NAC), such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes. Patients with luminal cancers do not appear to derive much clinical benefit from NAC, but some may appear to be sensitive to anti-programmed death-ligand 1 (PDL1) antibodies and possibly other immune checkpoint inhibitors. It is hoped that future studies will also identify biomarkers such as immunohistochemical markers which may be used to predict therapeutic response of these tumors. This will contribute substantially toward efficient and cost-effective diagnosis and management of these neoplasms.	bladder